PMID:22383684

Citation	Badin, PM, Loubière, C, Coonen, M, Louche, K, Tavernier, G, Bourlier, V, Mairal, A, Rustan, AC, Smith, SR, Langin, D and Moro, C (2012) Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58. J. Lipid Res. 53:839-48
Abstract	We investigated here the specific role of CGI-58 in the regulation of energy metabolism in skeletal muscle. We first examined CGI-58 protein expression in various muscle types in mice, and next modulated CGI-58 expression during overexpression and knockdown studies in human primary myotubes and evaluated the consequences on oxidative metabolism. We observed a preferential expression of CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase activity. We next showed by pulse-chase that CGI-58 overexpression increased by more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG-derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing reduced TAG hydrolysis and TAG-derived FA release and oxidation (-77%, P < 0.001), whereas it increased glucose oxidation and glycogen synthesis. Interestingly, modulations of CGI-58 expression and FA release are reflected by changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation involves the activation of the peroxisome proliferator activating receptor-δ (PPARδ) by lipolysis products. Altogether, these data reveal that CGI-58 plays a limiting role in the control of oxidative metabolism by modulating FA availability and the expression of PPARδ-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle.
Links	PubMed PMC3329383 Online version:10.1194/jlr.M019182
Keywords	1-Acylglycerol-3-Phosphate O-Acyltransferase/deficiency; 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics; 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism; Adolescent; Animals; Cells, Cultured; Energy Metabolism; Fatty Acids/metabolism; Gene Expression Regulation, Enzymologic; Gene Knockdown Techniques; Glucose/metabolism; Humans; Hydrolases/metabolism; Lipase/metabolism; Lipolysis; Mice; Mitochondria/metabolism; Muscle Fibers, Skeletal/cytology; Muscle Fibers, Skeletal/metabolism; Muscle, Skeletal/enzymology; Muscle, Skeletal/metabolism; Oxidation-Reduction; PPAR delta/metabolism; Triglycerides/metabolism; Young Adult
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ABHD5		GO:0050996: positive regulation of lipid catabolic process	ECO:0000315:		P		Figure 4	complete CACAO 3960
MOUSE:ABHD5	involved_in	GO:0050996: positive regulation of lipid catabolic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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